1. Field of the Invention: This invention relates generally to apparatus and method for treating cancerous tissue through hyperthermia thermotherapy, and more particularly to an improved thermoseed exhibiting a combination of properties, such that when subjected to an oscillating magnetic field of a predetermined frequency and field strength, produces controlled heating of the tissue into which such seeds are implanted.
2. Discussion of the Prior Art: In a journal article entitled "Practical Aspects of Ferromagnetic Thermoseed Hyperthermia", published in the Radiologic Clinics of North America, Vol. 27, No. 3, dated May 1989, Ivan A. Brezovich and Ruby F. Meredith, both then with the University of Alabama at Birmingham, presented a general treatise on a method of treating tumors by interstitially implanting small pieces of ferromagnetic alloy wire into the tissue and then exposing the subject to an externally applied oscillating magnetic field of a predetermined frequency and field strength so as to cause inductive heating of the thermoseeds within the body. This paper points out that by selecting a ferromagnetic material having a proper Curie point, such thermoseeds become self-regulating when the temperature of the seed approaches the Curie point at which the material becomes non-magnetic. The Brezovich et al. paper further points out that while ferromagnetic elements, such as iron, nickel and cobalt have Curie points far above the therapeutic range, the Curie point can be lowered by mixing a non-magnetic element into a ferromagnetic base metal. Nickel mixed with palladium, copper and silicon as well as iron mixed with platinum are suggested.
The Borrelli et al. patent 4,323,056, assigned to Corning Glass Works, and entitled "Radio Frequency Induced Hyperthermia for Tumor Therapy", describes a method in which magnetic field suscepting crystals of a certain size, composition, concentration, and magnetic properties are injected into the cancerous tissue and then the area involved is subjected to a high frequency magnetic field to effect hysteresis heating and resultant hyperthermia. In particular, the patent discloses the use of iron-containing crystals incorporated into certain organic plastics used as a matrix.
Our research is shown that while iron and nickel alloys have been widely studied and candidates for thermoseeds in cancer treatment, cobalt alloys have not received significant attention for a number of reasons. First, the Curie temperature of cobalt is 1130.degree. C. compared to values of 358.degree. C. and 770.degree. C. for nickel and iron, respectively. This is believed to explain why so much attention has been devoted to the study of nickel binary alloys. According to metallurgical theory of magnetic alloys, nonmagnetic additions to ferromagnetic elements should lower the magnetization (magnetic permeability) of the material, as well as lowering the Curie temperature. Thus, alloys with low Curie points will have significantly poorer magnetic properties, corresponding to less heating power output below the Curie point for thermoseeds. Since nickel has the lowest initial Curie point, there will need to be lesser amounts of non-magnetic impurity need be added to bring the Curie temperature to the therapeutic range. Thus, following that logic, nickel alloys should retain their magnetic permeability better than iron or cobalt.
In addition to Curie point depression and magnetic permeability decline, non-magnetic additives to ferromagnetic elements tend to broaden the Curie transition from a few degrees C., to tens of degrees. A 1938 French scientist, Victor Marian, conducted numerous analyses of nickel alloys and found that many of the alloys had transitions of 50.degree. C. to 100.degree. C. when the ferromagnetic component was reduced to a few percent. This is believed to be the reason why, until now, other investigators have used nickel silicon alloy for their thermoseed experiments, as only 7% silicon reduces the Curie point of its alloy with nickel to 50.degree. C. which is in the therapeutic range, while maintaining a fairly sharp Curie transition.
We have found that a cobalt palladium (CoPd) alloy does not match the standard pattern of binary magnetic alloys due to polarization of the palladium atoms. Even if as little as 5% Co is present, the magnetic transition of the alloy is still on the order of only 2.degree. C.-3.degree. C. and significant magnetization, and therefore heating power, is retained until the transition zone is reached. However, the magnetic permeability of the CoPd material is not as strong as for some of the other materials which have been the subject of investigation for use as thermoseeds.
Experiments that we have conducted, in which the magnetization of the CoPd alloy is plotted against temperature, reveals an interesting and rather unexpected result. Specifically, the permeability of this alloy is found to increase with heating in a range below the Curie point until the Curie transition is reached. As a result, implants fabricated from the alloy and the external field generator can be designed so that the seeds will radiate increasing amounts of power as they heat, until the Curie transition point is reached. By optimizing the implant about this local peak in the M vs. T curve, a highly efficient on-off switch can be constructed, with maximum power output within a few degrees of the Curie transition. This performance is not possible with other alloys, such as nickel copper, as its M vs. T curve decreases continuously with temperature.
The use of thermoseeds to heat tissue involves implanting an array of small (approximately 0.5 mm radius, 1 cm or more long) ferromagnetic seeds directly into the tissue. When the seeds are placed in an alternating magnetic field, heat is produced. The seeds may be left in the body following treatment so there is no need for further invasive procedures following implantation to extract them. Given the fact that the thermoseeds are to remain in the body, it is necessary to consider the potential toxicity of the ferromagnetic alloy employed. The toxicity of nickel has been well established. Severe allergic reactions among humans can result from contact with nickel and can cause hemolysis of human red blood cells through an apparent direct interaction between the red cell membrane and the Ni particle surface. The occurrence of copper toxicity, while somewhat infrequent, remains a problem. Acute copper poisoning can result in severe intravascular hemolysis resulting in jaundice and acute renal failure.
In that CoPd alloy has been in the past as an implantable substance, especially in dental prostheses, extensive toxicity evaluations have been made on the material revealing that such a binary alloy has only very weak cytotoxicity as compared to nickel and copper alloys.
It is accordingly a principal object of the present invention to provide a new thermoseed for use in treatment of tumors.
Another object of the invention is to provide a thermoseed formed from a ferromagnetic alloy that exhibits an increasing magnetization with temperature characteristic until its Curie point temperature is approached as the thermoseed is inductively heated upon exposure to an oscillating magnetic field.
Yet another object of the invention is to provide an inductively heated thermoseed comprised of an alloy that does not readily corrode in body fluids and is relative non-toxic.
Still another object of the invention is to provide a thermoseed formed from an alloy of cobalt and palladium where the percent of palladium in the alloy positions the Curie point within a therapeutic range without.-unduly broadening the Curie transition range.